Among microbiotic metabolites having a triprenyl phenol skeleton, there are species having important physiological activities. For example, specific triprenyl phenol compounds obtained from filamentous fungi are known to have physiologically active effects on phenomena that are important to the living body, such as a thrombolysis enhancing action or an angiogenesis suppressive action (Patent Documents 1 to 3).
Furthermore, as another triprenyl phenol compound differing from the above-mentioned triprenyl phenol compounds in stereostructure, Patent Document 4 discloses a triprenyl phenol compound having hair growth activity. Non-Patent Document 1 also discloses a triprenyl phenol compound having antibacterial activity and antifungal activity.
It has been suggested that triprenyl phenol compounds obtained from cultures using filamentous fungi induce changes in the conformation of plasminogen (Plg), and as a result, increase sensitivity to activation by plasminogen activators (PA) and the ability of plasminogen to bind fibrin, thus enhancing thrombolysis (Non-patent Document 2). A compound having two triprenyl phenol skeletons, which is obtained by adding ornithine as the amino acid (hereinafter, referred to as orniplabin), is, in particular, known to have a significantly strong thrombolysis enhancing action (Patent document 2).
In this way, since compounds having a triprenyl phenol skeleton exhibit a variety of activities in accordance with their stereostructure or substituents, the compounds are extremely useful.
These triprenyl phenol compounds having various activity types have complicated structures, and thus there is demand for a method to obtain the compounds more efficiently. As such a production method, methods for producing the compounds by culturing microorganisms are being developed. However, in methods using microorganisms, typically, the compounds are produced together with numerous analogs and, therefore, various measures are being implemented so as to obtain the compounds efficiently in large amounts. In particular, in order to produce active triprenyl phenol compounds having physiological activities such as a thrombolysis enhancing action or an angiogenesis inhibitory action, Patent Documents 1 to 3 disclose a culture system to which an amino acid or amino alcohol corresponding to the substituent is added during the early phase of the culture of filamentous fungi, such as immediately after the initiation of culture.    Patent Document 1: Japanese Patent Application Laid-Open (JP-A) No. 2002-65288    Patent Document 2: JP-A No. 2004-224737    Patent Document 3: JP-A No. 2004-224738    Patent Document 4: International Patent Publication WO 98/56940    Non-Patent Document 1: J. Org. Chem., (1992), Vol. 57, pp. 6700-6703    Non-Patent Document 2: FEBS Letter, (1997), Vol. 418, pp. 58-62